Rosuvastatin is generic name for (+)-7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl]-(3R,5S)-dihydroxy-(E)-heptenoic acid administered in the therapy as its calcium salt as commercial drug, and illustrated in Formula 1 hereinafter, which compound is an inhibitor of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG CoA reductase), useful in the treatment of hyperlipidemia, hypercholesterolemia and atherosclerosis. Rosuvastatin and the synthesis of rosuvastatin calcium was first disclosed in patent EP-B-521 471; in the last two steps of the whole synthesis provided by hydrolysis of methyl ester of rosuvastatin (methyl rosuvastatin) in polar solvent, e.g. ethanol, in the presence of a base, following by isolation of sodium salt of rosuvastatin (sodium rosuvastatinate) and converting said sodium salt of rosuvastatin with a water soluble calcium salt under aqueous conditions to calcium salt of rosuvastatin. The process for the preparation of the intermediates disclosed in EP-B-521 471 patent is incorporated herein by reference.
WO 2005/023778 discloses a process for the preparation of rosuvastatin calcium by conversion of C1 to C4 alkyl ester of rosuvastatin, preferably tert-butyl ester of rosuvastatin with a base, preferably sodium hydroxide, in the presence of a C1 to C4 alcohol, preferably ethanol, to a solution of rosuvastatin salt, e.g. its sodium salt and converted said salt into rosuvastatin calcium by adding a source of calcium to said solution.
A novel crystalline form of rosuvastatin calcium can be prepared by crystallization of amorphous form of rosuvastatin calcium from a mixture of: (i) water and acetonitrile in the ratio of 1:1 by volume; (ii) water and acetone in the ratio of 1:1 by volume; or water, methanol and tert-butyl methyl ether in the ratio of 1:1:1 by volume, what is described in WO 2000/042024.
WO 2005/040134 describes amorphous rosuvastatin calcium having a purity of more than 99% obtained from known crystalline rosuvastatin calcium. Said crystalline form may be prepared by crystallization of amorphous rosuvastatin calcium which process is known from the prior art.

It is well known that alkali metal salts of organic carboxylic acids are often hygroscopic what may cause problems at isolation. Indeed the isolation of sodium salt of rosuvastatin, which can be an intermediate in preparing rosuvastatin calcium salt, might be unrepeatable in yield and physical state what depends on the reaction conditions and evaporation of solvents, which is difficult to control. International publication WO 05/23778 tried to avoid said problems without isolating rosuvastatin sodium salt by extraction of impurities from its aqueous solution, but by using C1 to C4 alcohols as reaction medium a risk of conversion into specific impurities still existed. Namely, it is known that β-hydroxy acids in alcoholic alkali solution are submitted to dehydration what may lead after realkoxylation into special side products (see the reaction Scheme of FIG. 1, wherein R and R1 independently denotes C1 to C5 alkyl group), O-alkyl rosuvastatin, e.g. O-ethyl rosuvastatin.
From the results of stress stability test photographed on FIG. 2 it is obvious that rosuvastatin was submitted to specific degradation in ethanol as alcoholic medium. The specific impurity, designated as NN 2047.143 is O-ethyl ether derivative (see the reaction Scheme of FIG. 1 wherein R denotes ethyl (Et) group), was detected in 0.35% area by HPLC in comparison with acetone solution in which no such impurity was observed.
Therefore a need for an efficient process for preparing pure rosuvastatin calcium, without any significant amounts of side products, still exists.